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An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design.
Herst, C V; Burkholz, S; Sidney, J; Sette, A; Harris, P E; Massey, S; Brasel, T; Cunha-Neto, E; Rosa, D S; Chao, W C H; Carback, R; Hodge, T; Wang, L; Ciotlos, S; Lloyd, P; Rubsamen, R.
Afiliación
  • Herst CV; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Burkholz S; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Sidney J; La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037, United States.
  • Sette A; La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037, United States.
  • Harris PE; Endocrinology Division, Department of Medicine, School of Medicine, Columbia University, New York, NY, USA.
  • Massey S; University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555, United States.
  • Brasel T; University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555, United States.
  • Cunha-Neto E; Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology (iii) INCT, São Paulo, Brazil; Heart Institute (Incor), School of Medicine, University of São Paulo, São Paulo, Brazil.
  • Rosa DS; Institute for Investigation in Immunology (iii) INCT, São Paulo, Brazil; Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
  • Chao WCH; University of Macau, E12 Avenida da Universidade, Taipa, Macau, China.
  • Carback R; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Hodge T; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Wang L; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Ciotlos S; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Lloyd P; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • Rubsamen R; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States; Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St, Boston, MA 02114, United States. Electronic address: reidrubsamen@alum.mit.edu.
Vaccine ; 38(28): 4464-4475, 2020 06 09.
Article en En | MEDLINE | ID: mdl-32418793
ABSTRACT
The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vacunas Virales / Linfocitos T Citotóxicos / Diseño de Fármacos / Epítopos de Linfocito T / Proteínas de la Nucleocápside / Vacunas de Subunidad / Vacunas contra el Virus del Ébola Límite: Animals / Humans Idioma: En Revista: Vaccine Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Vacunas Virales / Linfocitos T Citotóxicos / Diseño de Fármacos / Epítopos de Linfocito T / Proteínas de la Nucleocápside / Vacunas de Subunidad / Vacunas contra el Virus del Ébola Límite: Animals / Humans Idioma: En Revista: Vaccine Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos